Vesicles, polypeptide-based

Historically, after the development of oligopeptide-based vesicles, several groups developed and characterized vesicles using polypeptide hybrid systems consisting of polypeptide and synthetic polymer blocks [17-19]. Soon thereafter, vesicles formed entirely from polypeptides, such as poly(L-lysine)-h-poly(L-leucine) and poly(L-lysine)-h-poly(L-glutamate), were developed [20, 21]. This review will focus on recent developments in the formation of vesicles composed of polypeptide hybrid or polypeptide systems, as well as the potential promise of these systems as effective dmg delivery vehicles. A specific example of a polypeptide-based vesicle is shown in Fig. 1, where the hydrophobic segment is a-helical and the hydrophilic segment is a random coil. 

Many polypeptide-based materials are able to self-assemble into vesicles when directly dissolved into the appropriate solvent. In fact, this method was used to form some of the earliest polypeptide vesicles in the literature. Lecommandoux and... 

Polymeric phospholipids based on dioctadecyldimethylammonium methacrylate were formed by photopolymerization to give polymer-encased vesicles which retained phase behavior. The polymerized vesicles were more stable than non-polymerized vesicles, and permeability experiments showed that vesicles polymerized above the phase transition temperature have lower permeability than the nonpolymerized ones [447-449]. Kono et al. [450,451] employed a polypeptide based on lysine, 2 aminoisobutyric acid and leucine as the sensitive polymer. In the latter reference the polypeptide adhered to the vesicular lipid bilayer membrane at high pH by assuming an amphiphilic helical conformation, while at low pH the structure was disturbed resulting in release of the encapsulated substances. 

The phase behaviour of biomimetic polypeptide-based copolymers in solution was described and discussed with respect to the occurrence of secondary structure effects. Evidently, incorporation of crystallisable polypeptide segments inside the core of an aggregate has impact on the curvature of the corecorona interface and promotes the formation of fibrils or vesicles or other flat superstructures. Spherical micelles are usually not observed. Copolymers with soluble polypeptide segments, on the other hand, seem to behave like conventional block copolymers. A pH-induced change of the conformation of coronal polypeptide chains only affects the size of aggregates but not their shape. The lyotropic phases of polypeptide copolymers indicate the existence of hierarchical superstructures with ordering in the length-scale of microns. 

Polymers are versatile building blocks for the synthesis of structured or-ganic/inorganic composite materials [66], Biohybrid or polypeptide-based vesicles, however, have scarcely been used for this purpose, only for the production or encapsulation of nanoparticles. 

Gebhardt KE, Ahn S, Venkatachalam G, Savin DA (2008) Role of secondary structure changes on the morphology of polypeptide-based block copolymer vesicles. J Colloid Interface Sci 317 70-76... 

Checot F, Rodiiguez-Hemandez J, Gnanou Y, Lecommandoux S. pH-responsive micelles and vesicles nanocapsules based on polypeptide diblock copolymers. Biomol Eng 2007 24 81-85. 

Even newer generations of nanomaterials are based on carbon nanotubes using the bottom-up approach. The materials are still very expensive, but the technology is evolving rapidly. Another type of nanotube has been prepared based on self-assembly of specific molecules such as chitosan-based nanoparticles of polypeptides, DNA or synthetic polymers. Phospholipids or dendrimer-coated particles are suitable for the entrapment of actives in very small vesicles. The current materials are still lacking in selectivity and yield (costs). 

Linear polypeptide block copolymers, block copolymers with pendent sugar or peptide grafts, and modified linear or dendritic homopolymers have been used to produce vesicles based on hydrophobic interactions and packing issues. Usually, the peptides or sugars make the minority hydrophilic part of the copolymers and are thus incorporated in the corona and not in the membrane of the vesicles. For the inverse case, the hydrophobic peptides in the membrane are often too short to adopt a stable secondary structure. 

A new polymeric amphiphile based on cationic poly(L-lysine), which was partially modified with hydrophobic palmitoyl chains and hydrophilic neutral methoxy-poly(ethylene glycol) (Fig. 7e), was introduced by Uchegbu et al. [38,39], In water in the presence of cholesterol, these copolymers assembled into vesicles with diameters ranging from 200 to 600 nm (DLS, freeze-fracture TEM), depending on the chemical composition of the copolymer and the length of the polypeptide backbone. More detailed information about the secondary structure of chains and the structure of vesicle membranes were not given. 

This conclusion is based on immunogold localization of PrP in these organelles by electron microscopy inhibition of PrP internalization by incubation of cells in hypertonic sucrose, which disrupts clathrin lattices and detection of PrP in purified preparations of coated vesicles from brain. The N-terminal half of the PrP polypeptide chain is essential for efficient clathrin-mediated endocytosis, because... 

Rodriguez-Hemandez J, Lecommandoux S (2005) Reversible inside-out miceUization of ph-responsive and water-soluble vesicles based on polypeptide diblock copolymers. J Am Chem Soc 127 2026-2027... 

The aim of this chapter is to give a brief selective overview of typical biomedical areas where cationic polymers can be employed. The use of cationic polymers in tissue engineering is a high priority topic in this chapter and several aspects on this phenomenon are given related to this is the potential of cationic hydrogels for medical and pharmaceutical applications. The importance of cationic polymers and copolymers as non-viral vectors in gene therapy is described, as well as how micelles and vesicles based on cationic polypeptides can form nanostructures by self-assembly. The potential of cationic polymers for drug delivery applications is also elucidated. 

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